Anionic bacterial membrane phospholipids

Anionic bacterial membrane phospholipids, primarily phosphatidylglycerol and cardiolipin, are fundamental structural components of the bacterial cell envelope (Epand & Epand, 2009, Biochimica et Biophysica Acta). These lipids create a negatively charged surface that distinguishes bacterial membranes from the predominantly neutral zwitterionic membranes of mammalian cells (Zasloff, 2002, Nature). This charge differential is exploited by various cationic antimicrobial peptides and lipopeptide antibiotics to achieve selective toxicity (Velkov et al., 2013, Future Microbiology). Upon binding, these drugs disrupt the lipid bilayer's integrity, causing rapid depolarization, loss of membrane potential, and leakage of essential ions and metabolites (Muller et al., 2016, Nature Communications). These phospholipids also serve as anchors for membrane proteins and are involved in the regulation of cell wall synthesis and cell division (Epand & Epand, 2009). Consequently, these phospholipids are critical targets in the treatment of severe infections caused by Gram-positive and Gram-negative pathogens, including multi-drug-resistant strains (Velkov et al., 2013). Resistance can emerge through the modification of these lipids, such as the addition of lysine or aminoarabinose, which reduces the net negative charge of the membrane (Muller et al., 2016).

Other names

Bacterial anionic phospholipidsNegatively charged bacterial lipidsPhosphatidylglycerolCardiolipinBacterial membrane bilayers

Cationic antimicrobial agents bind to anionic phospholipids via electrostatic interactions, leading to membrane insertion, pore formation, depolarization, and leakage of cytoplasmic contents (Muller et al., 2016; Velkov et al., 2013).